| First Author | Swain SD | Year | 2014 |
| Journal | Am J Pathol | Volume | 184 |
| Issue | 2 | Pages | 483-93 |
| PubMed ID | 24361497 | Mgi Jnum | J:206386 |
| Mgi Id | MGI:5550177 | Doi | 10.1016/j.ajpath.2013.10.027 |
| Citation | Swain SD, et al. (2014) CD4+ T cells and IFN-gamma are required for the development of Pneumocystis-associated pulmonary hypertension. Am J Pathol 184(2):483-93 |
| abstractText | Pulmonary hypertension (PH) is a disease of diverse etiology. Although primary PH can develop in the absence of prior disease, PH more commonly develops in conjunction with other pulmonary pathologies. We previously reported a mouse model in which PH occurs as a sequela of Pneumocystis infection in the context of transient CD4 depletion. Here, we report that instead of the expected Th2 pathways, the Th1 cytokine IFN-gamma is essential for the development of PH, as wild-type mice developed PH but IFN-gamma knockout mice did not. Because gene expression analysis showed few strain differences that were not immune-function related, we focused on those responses as potential pathologic mechanisms. In addition to dependence on IFN-gamma, we found that when CD4 cells were continuously depleted, but infection was limited by antibiotic treatment, PH did not occur, confirming that CD4 T cells are required for PH development. Also, although CD8 T-cells are implicated in the pathology of Pneumocystis pneumonia, they did not have a role in the onset of PH. Finally, we found differences in immune cell phenotypes that correlated with PH, including elevated CD204 expression in lung CD11c(+) cells, but their role remains unclear. Overall, we demonstrate that a transient, localized, immune response requiring IFN-gamma and CD4-T cells can disrupt pulmonary vascular function and promote lingering PH. |
